The use of Karnofsky Performance Status (KPS) as a predictor of 3 month post discharge mortality in cirrhotic patients.

Aim
Is Karnofsky Performance Status (KPS) a predictor of 3 month post discharge mortality in cirrhotic patients?


Background
Cirrhotic patients often experience an abrupt decline in their health, which often leads to frequent hospitalization and can cause morbidity and mortality. Various models are currently used to predict mortality in cirrhotics however these have their limitations. The Karnofsky Performance Status (KPS) being one of the oldest performance status scales, is a health care provider-administered assessment that has been validated to predict mortality across the elderly and in the chronic disease populations.


Methods
We used the KPS performance status scale to envisage short-term mortality in cirrhotic and HCC patients who survive to be discharged from hospital.


Results
Our study showed that KPS one week post-discharge, child pugh score, hospital stay, international normalized ratio, serum albumin, total bilirubin and serum creatinine showed statistical significance on univariate analysis. On multivariate analysis, KPS was found to be statistical significant predictor of 3-month mortality.


Conclusion
Hence KPS can be utilized to identify cirrhotic patients at risk of 3-month post discharge mortality.


Introduction
Hospitalization is a marker of poor outcomes including readmission and death. Patients with cirrhosis experience abrupt deterioration in their health that leads to repeated hospitalizations along with increased morbidity and mortality (1)(2)(3). Currently, the models used to predict mortality in cirrhotics are liver-specific and kidney-specific prognostic indicators such as the Model for End-Stage Liver Disease (MELD) score (4). However the MELD score has several limitations (5-7) one of them being its lack of ability to account for an individual's performance status. It is now a well-known fact that performance status and the linked concept of infirmity are strong predictors of adverse outcomes in patient populations (8)(9)(10)(11)(12)(13)(14) including cirrhosis (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) and it often outperforming established prognostic markers (19)(20). The Karnofsky Performance Status (KPS) is a health care provider-administered assessment that takes 1-2 minutes to assign a patient to one of the 10 categories (ranging from 0 [dead] to 100 [normal activity, no evidence of disease]). It is one of the oldest performance status scales (21) and has been validated to predict mortality across elderly and chronic disease populations (22)(23)(24). Orman et al identifying the KPS, independent of the liver function, as a predictor of liver transplant waiting list mortality (16). Thus KPS has been shown to be an important, user-friendly screening modality for an additional general risk stratification that can be readily administered in any clinical setting. In addition to being practical and easy to use, the validity and reliability of the KPS are well established (24)(25)(26).

ORIGINAL ARTICLE
Therefore the need to establish a practical prognostic model that could identify those at the highest risk of 3months mortality lead us to validate the KPS as a prognostic predictor in our patient populations (those with cirrhosis and hepatocellular carcinoma).Since this would assist us in selecting patients who need a more intensive follow-up and consideration of early liver transplant when available. Furthermore, an assessment of the probability of survival could help us update the type of palliative support that is provided to patients.

Methods
Cirrhotic patients of either gender were prospectively enrolled non-electively in this study conducted at the Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan, a large tertiary care centre located in Pakistan's largest city Karachi. These patients were followed for 3 months throughout their hospitalization or after discharge by using systematic phone calls, during outpatient visits and interviewed to evaluate for outcomes either within the hospital or elsewhere (1,27) Patients were recruited from June 2016 until July 2017. A diagnosis of cirrhosis was established by endoscopic or radiological evidence of portal hypertension or cirrhosis, compatible biopsy findings, and/or signs of hepatic decompensation, including hepatic encephalopathy (HE), jaundice, variceal bleeding, and ascites. Patients who failed to give informed consent, those who were transplanted during hospitalization and those with metastatic cancer (excluding Hepatocellular Carcinoma), human immunodeficiency virus, or inability to obtain KPS assessment at 1 week after hospital discharge were excluded. Data were collected regarding patient demographics, liver disease etiology and severity (MELD and Child-Pugh scores), admission variables (admission indication, cirrhosis complications and organ failures occurring during hospitalization, length of stay), and discharge variables (laboratory results, medications). At 1 week post discharge, the research assistant assessed the patient's KPS using questions directed to the patient and the caregiver in a telephonic interview. The KPS score was categorized into low (score 10-40), intermediate (50-70), and high (80-100) (16). Subjects were followed for 3 months post discharge systematically to evaluate health outcomes. The collected data were entered into SPSS (version 20.0) and analyzed by the researcher. Mean and standard deviation were calculated for continous variables. Frequency and percentages were calculated for categorical variables. Models for the prediction of 3month mortality were based on variables measured at baseline, during the index stay, on the date of discharge from the index admission, and KPS at 1 week post discharge. A p value < 0.05 was considered significant.
On multivariate analysis, KPS (p=0.016) was found to be statistical significant predictor of 3-month mortality.
After stratifying data for the presence of HCC, univariate analysis had statistical significance with KPS one week post-discharge (p= 0.00), Child class score (p=0.04), international normalized ratio (p=0.04) and serum albumin (p=0.000). On multivariate analysis, KPS (p= 0.34) and serum albumin (p=0.016) were found to be a statistical significant predictor of 3-month mortality after discharge.

Discussion
In cirrhotic patients accurate prognostication is indispensable because it guides us to prescribe the type and decide about the frequency of clinical care and helps us inform patients and their families about their possible outcomes. To our information, this is the first single center prospective study done in Pakistan using a performance status scale(KPS) to envisage short-term mortality in cirrhotic and HCC patients who survive to be discharged from hospital. Our study is in accord with Tandon et al (28) who also documented similar finding in their study by using the same KAM model. This also extends the results of the recently done retrospective study done by Orman et al. 16 and Tapper et al, (15) identified activities of daily living score done at hospital admission as a predictor of either 90-day in-hospital or post discharge mortality.
In routine clinical practice the addition of the KPS has been found to be highly reproducible and predictive in cirrhosis seen during outpatient visits, even when compared to the other more lengthy performance status evaluations such as the Fried Frailty Scale and the Short Physical Performance Battery (18). As estimated of a hospitalized population, the scores in our cohort were significantly worse than those noted in the transplant waiting list study by Orman et al. (16) At 1 week post-hospital discharge, 33% of patients were in the high performance status range at 1 week posthospital discharge. Forty-five percent had intermediate scores, reflecting incapability to work and a requirement of support for personal needs. Only 21% of patients had a low KPS score, consistent with lack of ability to care for oneself and the need for the equivalent of institutional care. The proper provision of support in this area may be a key factor in reducing the astonishing rates of rehospitalization in this population (1). The poor performance status of this group supports the significance of a multidisciplinary approach prior to discharge these patients. We have also seen similar findings in HCC group i.e. those who had low KPS scores at 1 week, they have a high 3 months mortality in our follow up. A low 1 week post discharge KPS score was predicted by child class score, hospital stay, international normalized ratio (INR), serum albumin, total bilirubin,  (30). The limitations of our study were that we did not assess the KPS on the day of hospital admission or on the day of discharge and as a result we were not capable to depict a change in the performance status. Secondly it was beyond the extent of our study to evaluate several factors previously related with post hospitalization functional decline, including the prehospitalization functional reserve or the nutrition and mobilization therapy provided in hospital. This can be the focus of follow-on studies. Lastly it was a single centre study and further studies will be needed to validate this association. Almost 41% of cirrhotic patients who survive until discharge die within 3 months after hospitalization. These patients can be identified using the KPS based performance status score. This easy-to-use measurement is strongly and independently linked with an increased hazard of mortality and could be adopted in practice to lead post discharge early interventions, as well as the integrated provision of vigorous and palliative management strategies.